3However, this is not consistent with the latest treatment guidelines2Introduction to ASAOne of the most widely used drugs of the 20th century1Taken by millions of patients worldwide for the treatment and prevention of CVD, and is the most widely tested antiplatelet drug1Has been (and is still) used for stroke prevention in AF1,2Traditionally considered a safe, but less effective, alternative to VKAs when anticoagulation is contraindicated, or for use in patients at low risk of stroke1,2However, this is not consistent with the latest treatment guidelines2ASA = acetylsalicylic acid; CVD = cardiovascular disease; VKA = vitamin K antagonist1. Dai Y, Ge J. Thrombosis 2012;2012:245037; 2. Camm AJ et al. Eur Heart J 2012;33:2719–47

22ASA ConclusionsAntiplatelet therapy should be considered only when patients refuse any OAC, or cannot tolerate OAC for reasons unrelated to bleedingIn the real world, antiplatelet therapy is still commonly prescribed for stroke prevention in AFCompared with ASA, NOAs (apixaban) significantly reduced the relative risk of stroke or systemic embolism by 55% while the risk of major bleeding was not significantly increasedThe evidence demonstrated that oral anticoagulation should be the preferred option in NVAF patients at risk of stroke

471509 patients after successful TAVI procedureATLANTIS trial: Apixaban in patients who underwent a clinically successful TAVI procedureSOC*-VKAStratum 1Indication for anticoagulationR1:1Apixaban 5mg twice daily 2.5 mg twice daily in select patients**1509 patients after successful TAVI procedure6 months of follow-upStratum 2No indication for anticoagulationR1:1SOC-DAPT/ SAPTPhase 4, randomised, open label, parallel group (N-1500)To asses whether anticoagulation with apixaban is not less safe than standard of care therapy in patients with valvular heart diseasefollowing transcatheter aortic valve implantation (TAVI)Primary endpointcomposite of death, myocardial Infarction, stroke/TIA/systemic emboli, intracardiac or bioprosthesis thrombus, episode of deep vein thrombosis or pulmonary embolism, major bleedings over 6 months of follow-up* Standard of Care** 2.5mg bid if creatinine clearance 15-29mL/min or if two of the following criteria: age ≥80 years, weight ≤ 60kg or creatinine ≥1,5mg/dL (133µMol)Design and execution of this trial is not yet finalized and may be subject to further changes

57Warfarin ConclusionsWarfarin will continue to be used in patients with mecanical prosthetic heart valve and patients with rheumatic valve diseaseWarfarin will continue to be used in patients with severe renal failureWarfarin will continue to be used in patients with drug-drug interactionsNOAs should be considered rather than adjusted-dose VKA for most patietns with NVAF, based on their net clinical benefit

58Assume that NAOs have been on the market for 5 yearA new drug comes to the market. Compared to NAOs, the new drug has:- cheaper- antidote- requirement for monthly monitoring to adjust dose- many food and drug interactions- 25% increased relative risk of stroke/systemic embolism- nearly 50% increased relative risk of major bleeding- approx. 2.5 times the rate of ICH- 10% increased relative risk of mortalityWould Warfarin be approved by regulatory authorities now?